A Copper-Free Sonogashira Coupling Reaction in Ionic Liquids and Its Application to a Microflow System for Efficient Catalyst Recycling

Abstract

[reaction: see text] The PdCl2(PPh3)2-catalyzed Sonogashira coupling reaction, in good to high yields, was performed in an ionic liquid ([BMIm][PF6]) in the absence of a copper salt. The use of an ionic liquid allows for the facile separation and recycling of the catalyst. The application of the above reaction in a microflow system in conjunction with an IMM micromixer was also successful.

Ionic Liquids within Microfluidic Devices

“…The excellent mass transfer characteristics within and between the catalyst carrier phase and reaction medium, together with the minimal catalytic pore diffusion resistances at the micrometer scale, make such biphasic catalysis an attractive alternative to conventional catalysis operation (Wieβmeier, 1996;Rahman et al, 2006). Several authors reported on successful Pd-catalyzed cross coupling reactions in ionic liquids within a microfluidic devices, such as Sonogashira reactions (Fukuyama et al, 2002;Rahman et al, 2006) and Mizoroki-Heck reactions (Liu et al, 2004). Fukuyama and his group conducted the first example of a homogeneous metal-catalyzed reaction in a microreactor ( Figure 6).…”

“…The coupling product diphenylacetylene was formed and was easily isolated from the mixture by extraction with hexane/water (93% yield). The resulting ionic liquid containing the Pd catalyst could be successfully reused for several times with only a slight loss in its activity (Fukuyama et al, 2002). Another successful application of [BMIM] [PF 6 ] ionic liquid supported catalytic microflow reactions for Pd-catalyzed carbonylative Sonogasnira coupling of aryl iodides and phenylacetylene was reported by Rahman et al (2006).…”

“…The coupling product (4a) was formed and was easily isolated by extraction with hexane/water. Adapted from Fukuyama et al (2002). Reproduced by permission of the American Chemical Society.…”

Rapid catalyst evaluation for Sonogashira coupling in continuous flow

“…For example the reaction was performed in an ionic liquid ([BMIm] [PF 6 ]) in the absence of a copper salt using PdCl 2 (PPh 3 ) 2 . 8 Kawanami applied high T/p water containing sodium hydroxide and palladium dichloride in a homogeneous microfluidic system (with fluid channels typically in the submillimeter range) applying residence time= 0.1-4.0 s, T= 250 °C , p= 160 bar. 9 In another homogenous flow approach Sugimoto applied a loop reactor (1000 μm i.d., 10 m length) mixing the alkyl halide and the alkyne in DMF and using PdCl 2 (PPh 3 ) 2 (1 mol %), CuBr (2 mol %), and diisopropylethylamine as a base at 120 °C.…”

Preparation of α-Bromoketones and Thiazoles from Ketones with NBS and Thioamides in Ionic Liquids

“…Ionic liquids offer interesting and useful features that are advantageous to organic reactions such as negligible vapor pressure, nonflammability, high thermal stability, and easy reusability. In this regard, ionic liquids have been successfully used in the Friedel-Crafts reaction [31][32][33], hydrogenation [34][35][36], Diels-Alder reactions [37][38][39], Mizoroki-Heck, Suzuki-Miyaura, Sonogashira, and olefin metathesis reactions [40][41][42][43][44], Michael additions [45], oxidation [46][47][48][49][50][51][52][53][54], condensation reaction [55][56][57][58][59], formation of imines [60], 1,2-rearrangement [61], esterification of carboxylic acids and carboxylates [62][63][64][65], Williamson ether synthesis [66][67][68][69][70][71][72], and the Grignard reaction [73,74]. We have reported efficient methods for the esterification of carboxylic acids and phosphonic acids with trialkyl orthoacetate in ionic liquid <...>…”